Increased gelatinase B/matrix metalloproteinase 9 (MMP-9) activity in a murine model of acute coxsackievirus B4-induced pancreatitis.
Infection of mice with coxsackievirus B4 results within days in a severe acute necrotizing pancreatitis, which resolves completely within weeks. Gelatinase B or matrix metalloproteinase 9 (MMP-9) has previously been shown to be involved in several models of pancreatitis, but its role in virus-induced pancreatitis has never been investigated. We here report that MMP-9 levels are markedly increased in the pancreas of mice that developed acute pancreatitis following infection with coxsackievirus B4. Moreover, using in situ zymography, we demonstrated that MMP-9 is active in vivo. Double immunohistochemical analysis revealed that macrophages and neutrophils were the cellular source of MMP-9. Extensive tissue rearrangements involving collagen turnover were observed, and these were associated with extensive pathology and resolution of the disease. In summary, this report demonstrates that acute coxsackievirus B4-induced pancreatitis involves the action of MMP-9, which is mainly originating from macrophages and neutrophils.
De Palma
Armando M
AM
Laboratory of Virology and Experimental Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Verbeken
Erik
E
Van Aelst
Ilse
I
Van den Steen
Philippe E
PE
Opdenakker
Ghislain
G
Neyts
Johan
J
D000681:Amylases / Q000097:blood; D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology / Q000473:pathology*; D029822:Enterovirus B, Human / Q000502:physiology*; D008049:Lipase / Q000097:blood; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils / Q000201:enzymology; D010179:Pancreas / Q000276:immunology / Q000473:pathology*; D010195:Pancreatitis / Q000276:immunology / Q000473:pathology*; D012367:RNA, Viral / Q000097:blood; D014766:Viremia
D012367:RNA, Viral; D008049:Lipase; D000681:Amylases; D020780:Matrix Metalloproteinase 9